Intranasal Ketamine for Depression in Adults: A Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials
This meta-analysis (s=6, n=858) found that (es)ketamine administrated intranasally (via the nose) led to quick antidepressant effects for those suffering from depression (MDD & TRD). Although the effect was most pronounced in the first 24 hours after administration (MADRS decreased by 9.96 points), the effects held up at 28 days (4.09).
Authors
- Wei, C.
- Wang, J.
- An, D.
Published
Abstract
Background
There is growing interest in glutamatergic agents as a treatment for depression, especially intranasal ketamine, which has become a hot topic in recent years. We aim to assess the efficacy and safety of intranasal ketamine in the treatment of major depressive disorder (MDD), especially treatment-resistant depression (TRD).
Methods
We searched Medline, EMBASE, and the Cochrane Library until April 1, 2020 to identify double-blind, randomized controlled trials with allocation concealment evaluating intranasal ketamine in major depressive episodes. Clinical remission, response, and depressive symptoms were extracted by two independent raters. The outcome measures were Montgomery-Asberg Depression Rating Scale (MADRS) score improved from baseline, clinical response and remission, dissociative symptoms, and common adverse events. The analyses employed a random-effects model.
Results
Data were synthesized from five randomized controlled trials (RCTs) employing an intranasal esketamine and one RCT employing intranasal ketamine, representing 840 subjects in parallel arms, and 18 subjects in cross-over designs (n = 858 with MDD, n = 792 with TRD). The weighted mean difference of MADRS score was observed to decrease by 6.16 (95% CI 4.44-7.88) in 2-4 h, 9.96 (95% CI 8.97-10.95) in 24 h, and 4.09 (95% CI 2.18-6.00) in 28 day. The pooled relative risk (RR) was 3.55 (95% CI 1.5-8.38, z = 2.89, and p < 0.001) for clinical remission and 3.22 (95% CI 1.85-5.61, z = 4.14, and p < 0.001) for clinical response at 24 h, while the pooled RR was 1.7 (95% CI 1.28-2.24, z = 3.72, and p < 0.001) for clinical remission and 1.48 (95% CI 1.17-1.86, z = 3.28, and p < 0.001) for clinical response at 28 day. Intranasal ketamine was associated with the occurrence of transient dissociative symptoms and common adverse events, but no persistent psychoses or affective switches.
Conclusion
Our meta-analysis suggests that repeated intranasal ketamine conducted a fast-onset antidepression effect in unipolar depression, while the mild and transient adverse effects were acceptable.
Research Summary of 'Intranasal Ketamine for Depression in Adults: A Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials'
Introduction
Major depressive disorder (MDD) is a prevalent and disabling condition with a substantial proportion of patients—approximately 30%—classified as treatment-resistant depression (TRD), typically defined as failure to respond to at least two adequate antidepressant trials. Earlier research established that sub‑anesthetic intravenous ketamine produces rapid, transient antidepressant effects, but the intravenous route poses practical limitations for long‑term treatment. Intranasal administration and the S‑enantiomer esketamine have therefore been investigated as more convenient alternatives. Steiger and colleagues set out to evaluate the efficacy, safety, and tolerability of intranasal ketamine formulations (predominantly esketamine) for unipolar major depressive episodes, with particular focus on TRD. The study is a systematic review and meta‑analysis of randomized, double‑blind, placebo‑controlled trials, aiming to synthesise effects on depressive symptoms (MADRS), clinical response and remission, dissociative symptoms, and common adverse events over short (hours to days) and longer (up to 28 days and beyond) timeframes.
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Study Details
- Study Typemeta
- Journal
- Compounds
- Topics
- APA Citation
An, D., Wei, C., Wang, J., & Wu, A. (2021). Intranasal Ketamine for Depression in Adults: A Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials. Frontiers in Psychology, 12. https://doi.org/10.3389/fpsyg.2021.648691
References (6)
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Berman, R. M., Cappiello, A., Anand, A. et al. · Biological Psychiatry (2000)
Iadarola, N. D., Niciu, M. J., Richards, E. M. et al. · Therapeutic Advances in Chronic Disease (2015)
Murrough, J. W., Iosifescu, D. V., Chang, L. C. et al. · American Journal of Psychiatry (2013)
Chen, X., Hou, X., Bai, D. et al. · American Journal of Psychiatry (2019)
Romeo, B., Choucha, W., Fossati, P. et al. · Psychiatry Research (2015)
Zanos, P., Moaddel, P. J., Morris, P. J. et al. · Nature (2016)
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